The goal of this project is to develop improved methods for diagnosing and treating human uveitis. Three studies of diagnosis are as follows: (1) We examine biopsy and pathology specimens from patients with uveitis and AIDS to develop improved diagnostic tests and to understand better the pathophysiology of inflammatory eye disease. Ongoing studies of intraocular lymphoma show that multiple vitrectomies or lumbar punctures are required to diagnose about one-third of the patients, Appropriate, prompt handling of pathology specimens by an experienced cytopathologist remains critical to making the correct diagnosis. (2) To improve methods for diagnosing ocular sarcoidosis, we test lacrimal gland and conjunctival biopsies for the presence of interferon-gamma; Kveim antigen; interleukins 2,3,4,6 and 8; and T-cell receptors believed to be specific for this disease. This year we retrospectively reviewed 46 patients with biopsy-proven sarcoidosis and 21 with uveitis. In patients with ocular involvement, the most sensitive diagnostic test was the pulmonary diffusing capacity (DLCO), which diminished in 78% of patients tested. Corticotropin-releasing hormone tests are performed on patients with uveitis to determine whether a defective hypothalamic-pituitary- adrenal axis is associated with increased risk for autoimmune ocular inflammatory disease. (3) Our study of animals with endotoxin-induced uveitis (EIU) showed that tumor necrosis factor alpha causes a paradoxical exacerbation of ocular disease. In the area of treatment, we have three projects: (1) We are continuing a masked, randomized crossover study to compare acetazolamide to placebo for the treatment of uveitic cystoid macular edema; to date 31 patients have been recruited. (2) Topically applied FK 50 was used to treat EIU in the rat. Ocular inflammation was reduced significantly in animals treated with topical FK 506 (0.3% and 0.5%) when compared with control animals, a finding that may be useful in the treatment of acute ocular inflammation in humans. (3) The optimal therapy for intraocular lymphoma remains unclear; however, previous studies suggest that untreated patients die within 1 year of diagnosis. Retrospective review of 11 patients with intraocular lymphoma treated with radiation, chemotherapy, or both showed substantial treatment-related mortality. In a joint protocol and the National Cancer Institute, we now are investigating alternative treatment regimens for central nervous system lymphoma.